Abstract

Uterine receptivity for the embryo is established and maintained through a series of precise cellular and molecular events, such as DNA methylation. There have been no studies to elucidate entire genome DNA methylation changes associated with embryo receptivity development of the endometrium (RE). In the present study, there was development of a complete genome-wide DNA methylome maps of the RE using whole-genome bisulphite sequencing and bioinformatics analysis. As many as 163.06 Gb of sequencing data averaging 81.53 Gb per sample were obtained for genome bisulphite sequencing of endometrium samples. There were distinct genome-wide DNA methylation patterns in pre-receptive endometrium (PE; Day 5 of gestation) and RE (Day 15 of gestation). There were as many as 16,467 differentially methylated regions (DMRs); 21,391 DMRs were less methylated in RE samples compared with PE samples (P-values ≤ 0.05 and |log2 (fold change)| ≥ 2). Compared with PE samples, methylation ratios of IGF2BP2, ACOX2, PTGDS, VEGFB and PTGDR2 genes were markedly less in RE samples (P-value ≤ 0.05 and |log2 (fold change)| ≥ 2). Conversely, in RE samples there was a markedly greater methylation ratio of IGFBP3 and IGF1R genes. The results of KEGG analysis indicated that these genes were involved in the signalling pathways for insulin, mitogen-activated protein kinase, gonadotropin-releasing hormone, vascular endothelial growth factor and progesterone-mediated oocyte maturation, which participated in differential regulation of goat endometrial development during receptive and prereceptive phases. The results of previous and the present study indicate resulting proteins of IGF2BP2, PTGDS, VEGFB, PGR, IGFBP3 and IGF1R gene expression may have important functions in regulating endometrial receptivity for the embryo.

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